Determinants of intracellular RNA pharmacokinetics Implications for RNA-based immunotherapeutics

作者：Kuhn Andreas N; Diken Mustafa; Kreiter Sebastian; Vallazza Britta; Tuereci Oezlem; Sahin Ugur^*

来源：RNA Biology, 2011, 8(1): 35-43.

DOI：10.4161/rna.8.1.13767

• RNA stability
• translation
• 5 ' cap
• poly(A) tail
• untranslated regions
• codon usage
• immunotherapy

RNAs with optimized properties are increasingly investigated as a tool to deliver the genetic information of complete antigens into professional antigen-presenting dendritic cells for HLA haplotype-independent antigen-specific vaccination against cancer. As the dose of the antigen and duration of its presentation are critical factors for generating strong and sustained antigen-specific immune responses, improvement of the immunobioavailability of RNA-based vaccines has been a recurrent subject of research. Substantial increase of the amount of antigen produced from RNA can be achieved by optimizing RNA stability and translational efficiency. Both features are determined by cis-acting elements in the RNA, namely the 5' cap, the poly(A) tail, and the sequence of the coding and non-coding regions, which interact with corresponding trans-acting factors. This article summarizes recent developments in identifying optimized RNA for expression of foreign proteins in dendritic cells, as well as their implications for immunotherapy based on antigen-encoding RNA.

• 出版日期2011-2